Vδ2neg γ δ T Cells, a Multi-Reactive Tissue Subset: from Innate to Adaptive Altered-Self Surveillance
Résumé
Human γδ T cells are usually considered to contribute to fast-acting local immune responses. Their somewhat limited T cell receptor (TCR) diversity implies that large subsets of γδ T cells share the capacity to respond to the same restricted set of antigens, rather than showing the fine specificity toward extremely diverse antigens, as is characteristic of αβ T cells. This has been well demonstrated for Vγ9Vδ2 T cells, particularly in non-human primate models. However, much less is known about the other subsets of γδ T cells, herein collectively called Vδ2neg γδ T cells. Most of these cells express the Vδ1 chain, some express the Vδ3 chain, and very few express the four remaining Vδ chains (Vδ4 to Vδ8). All these Vδ chains can be associated with any of the six Vγ chains (Vγ2, 3, 4, 5, 8, 9). Vδ2neg γδ T cells are mainly located in epithelial tissues and the spleen, and are barely found in the circulation in normal physiological conditions. This tissue localization has limited their analysis. Establishment of murine models is difficult since murine and human γδ T cell populations vary greatly. For example, the equivalent of murine dendritic epithelial γδ T cells (DETC) does not exist in humans, and conversely, the equivalent of human Vγ9Vδ2 T cells is present only in primates. Therefore, human Vδ2neg γδ T cells have mostly been examined during pathological situations where their circulating levels are increased. Like Vγ9Vδ2 T cells, Vδ1 and Vδ3 T cells have been shown to be involved in widely diverse pathological contexts, such as infection, cancer, auto-immunity, and inflammation. This suggests that γδ T cells respond to a variety of altered microenvironments induced by these situations. It is acknowledged that γδ T cells can recognize ubiquitous stress-induced conserved antigens in their native form, and altered-self or foreign ligands presented on non-polymorphic molecules in total independence of classical MHC molecules. Since Vδ2neg γδ T cells can recognize broadly distributed antigens and are localized at the interface with the outer environment within epithelial tissues, Vδ2neg γδ T cells can act as a first line of defense in the surveillance of body integrity and microorganism infections. Nevertheless, Vδ2neg γδ T cells can also display effector/memory phenotypes similar to conventional MHC-restricted αβ T cells. This suggests an ability to mount long-lasting anamnestic immunity similar to conventional αβ T cells. Here, we will review what is currently known about Vδ2neg γδ T cells highlighting the pathological situations where they expand. We will also discuss what is known concerning the cellular and molecular mechanisms of their activation and their effector functions.